Ageing compromises mouse thymus function and remodels epithelial cell differentiation

Jeanette Baran-Gale, Michael D Morgan, Stefano Maio, Fatima Dhalla, Irene Calvo-Asensio, Mary E Deadman, Adam E Handel, Ashley Maynard, Steven Chen, Foad Green, Rene V Sit, Norma F Neff, Spyros Darmanis, Weilun Tan, Andy P May, John C Marioni, Chris P Ponting, Georg A Holländer

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Ageing is characterised by cellular senescence, leading to imbalanced tissue
maintenance, cell death and compromised organ function. This is first observed in the thymus, the
primary lymphoid organ that generates and selects T cells. However, the molecular and cellular
mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse
ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T
cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing,
we find that progenitor cells are the principal targets of ageing, whereas the function of individual
mature thymic epithelial cells is compromised only modestly. Specifically, an early-life precursor cell
population, retained in the mouse cortex postnatally, is virtually extinguished at puberty.
Concomitantly, a medullary precursor cell quiesces, thereby impairing maintenance of the
medullary epithelium. Thus, ageing disrupts thymic progenitor differentiation and impairs the core
immunological functions of the thymus.
Original languageEnglish
Number of pages27
Publication statusPublished - 25 Aug 2020


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